This application proposes the addition of a Neuroimaging Core (NIC) to the newly established Alzheimer?s Disease Core Center (ADCC) at Wake Forest School of Medicine. The NIC will address a critical need to establish biomarkers that reliably differentiate Alzheimer?s disease (AD) from other conditions that affect cognition in aging. Recently, an AD research framework was developed for a biologically-based classification to enhance identification of disease mechanisms, to appropriately target therapeutic interventions, and to track therapeutic response and disease progression. Neuroimaging techniques, such as magnetic resonance imaging (MRI) to measure structural changes and positron emission tomography (PET) to track changes in pathological hallmarks such as b-amyloid and tau, comprise a powerful approach to characterize the progressive pathology associated with cognitive decline and to differentiate AD from other dementias. To establish reliable biomarkers associated with AD and other conditions that impair cognition with aging will require a large collaborative effort and the national NIH ADC network is ideally suited to address this need. The Wake Forest ADCC can make unique contributions to the network; the NIC will conduct longitudinal, multimodal neuroimaging paired with phenotypic and genomic characterization of a diverse cohort of participants. The NIC will provide expertise and resources to complement the ADCC themes, which focus on: 1) early transitions from normal aging to mild cognitive impairment (MCI) and AD; 2) the role of metabolic and vascular risk in these transitions; and 3) ethnic differences modulating these relationships. The first aim of the NIC will be to leverage existing Clinical Core and imaging infrastructure, including research-dedicated PET and MRI, cyclotron, and advanced analytic pipelines to help identify the causes of AD and develop novel strategies for prevention and treatment. As a second aim, the NIC will optimize participation of underrepresented groups in neuroimaging protocols, with a special focus on African-Americans, to better understand and reduce disparities in their risk of AD and other dementias. The third aim will be to expand interactions with the ADC network and NACC, and with institutional partners through aligned neuroimaging methods and new collaborations. The final aim will be to provide training and consultation on the latest scientific advances in neuroimaging to ADCC-affiliated investigators. Through these aims, the Wake Forest ADCC NIC will further the understanding of AD pathology and its relationship to cognitive decline and will significantly enhance the Center?s contribution to the ADC network and to investigators worldwide.